A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 Versus Placebo as Part of a Treatment Regimen Including Peginterferon α-2a (Pegasys®) and Ribavirin (Copegus®) or Peginterferon α-2b (PegIntron®) and Ribavirin (Rebetol®) in Treatment-naïve, Genotype 1, Hepatitis C-infected Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 393
- 主要终点
- The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
研究概览
简要总结
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in participants who are infected with genotype 1 hepatitis C virus who have never received treatment before. Participants will also receive peginterferon alfa-2a or peginterferon alfa-2b and ribavirin as part of their treatment.
详细描述
This is a randomized, double-blind (neither physician or participant knows the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus who have never received treatment for this before. Participants in this study will also receive two other drugs for their infection (either peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) or peginterferon alfa-2b (PegIntron®) and ribavirin (Rebetol®). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, participants will take TMC435 or placebo, plus peginterferon and ribavirin. For the next 12 weeks, participants will take peginterferon and ribavirin only. After that, some participants will continue to take peginterferon and ribavirin for up to 24 additional weeks. Other participants will stop taking peginterferon and ribavirin. The study doctor will inform each participant about how to take their study medication and when they should stop taking it. After a participant stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Participants will be monitored for safety throughout the study. Study assessments at each study visit may include but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), participant questionnaires, and physical examinations. TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Peginterferon (PegIntron®) will be given as an injection once each week and the dose will depend on your body weight. Ribavirin will be taken as a tablet (Copegus ®) or a capsule (Rebetol ®) twice each day and the dose will depend on your body weight.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genotype 1 hepatitis C infection (confirmed at screening)
- •Participant has not received any prior treatment for hepatitis C
- •Participant must have had a liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
- •Must agree to use 2 forms of effective contraception throughout study (both males and females)
排除标准
- •Infection with HIV or non genotype 1 hepatitis C
- •Liver disease not related to hepatitic C infection
- •Hepatic decompensation
- •Significant laboratory abnormalities or other active diseases
- •Pregnant or planning to become pregnant
研究组 & 干预措施
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 24 or 48 weeks
干预措施: TMC435 (Drug)
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 24 or 48 weeks
干预措施: Peginterferon alpha-2a or Peginterferon alpha-2b (PegIFNα-2a/b) (Drug)
TMC435
TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 24 or 48 weeks
干预措施: Ribavirin (RBV) (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 48 weeks
干预措施: Placebo (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 48 weeks
干预措施: Peginterferon alpha-2a or Peginterferon alpha-2b (PegIFNα-2a/b) (Drug)
Placebo
Placebo 150 mg capsule once daily for 12 weeks in addition peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 48 weeks
干预措施: Ribavirin (RBV) (Drug)
结局指标
主要结局
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
时间窗: Week 36 or Week 60
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
次要结局
- Percentage of Participants With Null Response(Week 12)
- The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)(Week 72)
- The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)(Week 48 or Week 72)
- The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)(Week 28 or Week 52)
- Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)(Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48)
- Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)(Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48)
- Percentage of Participants With On-treatment Virologic Response at All Time Points(Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42)
- The Percentage of Participants Achieving a Rapid Virologic Response (RVR)(Week 4)
- The Percentage of Participants Achieving a Early Virologic Response (EVR)(Week 12)
- The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)(Week 12)
- The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)(Weeks 4 and 12)
- The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4(Week 4)
- Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4(Week 4)
- Percentage of Participants With Partial Response(Week 12)
- Percentage of Participants With Viral Breakthrough(Up to Week 48)
- Percentage of Participants With Viral Relapse(Up to Week 72)
- Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule(Week 24)
- Percentage of Participants With On-treatment Failure(Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable(Up to Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable(Up to Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL(Up to Week 48)
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL(Up to Week 48)
- The Percentage of Participants With Viral Breakthrough at Different Time Points(Up to Week 48)
- Time From End-of-treatment to Viral Relapse(Up to Week 72)
- Plasma Concentration of TMC435: Systemic Clearance (CL)(At protocol-specified time points at Weeks 2, 4, 8, and 12)
- The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)(Up to Week 48)
- Median Time to Normalization of Alanine Aminotransferase (ALT) Levels(Up to Week 48)
- Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)(At protocol-specified time points from the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12)
- Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)(Blood samples tested were taken before administration of TMC435 and at 2 random time points after dosing (taken atleast 2 hours apart from each other) at Week 2, 4, 8, and 12)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores(Baseline to Week 60 and Week 72)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment(Baseline to Week 60 and Week 72)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment(Baseline to Week 60 and Week 72)
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment(Baseline to Week 60 and Week 72)